Study of the Safety and Contraceptive Efficacy of Relugolix Combination Therapy in Women With Uterine Fibroids or Endometriosis Who Are at Risk for Pregnancy

Contraception Clinical Trial

— SERENE  

Official title:

A Phase 3, Single-Arm, Open-Label Study to Evaluate the Safety and Contraceptive Efficacy of Relugolix Combination Therapy in Women With Uterine Fibroids or Endometriosis Who Are 18 to 50 Years of Age and at Risk for Pregnancy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04756037
• Other study ID #: MVT-601-050
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: March 18, 2021
• Est. completion date: February 2026

Study information

• Verified date: March 2024
• Source: Sumitomo Pharma Switzerland GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the contraceptive efficacy of relugolix combination therapy.

Description:

This is a single-arm, open-label, phase 3 study to assess the contraceptive efficacy of relugolix combination therapy (relugolix 40 milligrams [mg], estradiol [E2] 1 mg, and norethindrone acetate [NETA] 0.5 mg).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1020
• Est. completion date: February 2026
• Est. primary completion date: February 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

Key Inclusion Criteria:

1. Is a premenopausal woman, 18 to 50 years of age.

2. Is at risk of pregnancy (that is, having heterosexual intercourse at least once per month) and is seeking contraception.

3. Has normal, regular menstrual cycles that are between 21 and 35 days in duration.

4. Has a diagnosis of uterine fibroids or endometriosis meeting either of the following criteria:

1. Diagnosis of uterine fibroids by confirmation of ultrasound performed in the last 2 years and patient report of heavy menstrual bleeding affecting quality of life.

2. Diagnosis of endometriosis and has had surgical or direct visualization (laparoscopy or laparotomy) and/or histopathologic confirmation of endometriosis, and the patient reports moderate, severe, or very severe pain during the most recent menses and/or during nonmenstrual portion of the cycle in the prior month

5. Is willing to use the study intervention as the sole method of contraception for 13 consecutive 28-day treatment cycles and does not intend to use any other form of contraception (for example, condoms).

Key Exclusion Criteria:

1. Is pregnant, or breastfeeding, or has breastfed in the last year.

2. Has a known history of infertility or sub-fertility.

3. Has presence or history of a venous thromboembolic event (for example, deep vein thrombosis, pulmonary embolism), an arterial thrombotic or thromboembolic event (for example, myocardial infarction, stroke, or peripheral arterial), or a transient ischemic attack, angina pectoris, or claudication.

4. Has a higher risk of arterial, venous thrombotic, or thromboembolic disorders.

5. Has a history of migraine with aura or focal neurological symptoms.

6. Has uncontrolled hypertension, diabetes with inadequate control, or multiple cardiovascular risk factors.

7. Has a history of clinically significant ventricular arrhythmias.

8. Has clinically significant liver disease, including active viral hepatitis or cirrhosis.

9. Has a history of pancreatitis associated with severe hypertriglyceridemia.

10. Has known human immunodeficiency virus (HIV) infection or high risk of contracting HIV.

11. Has a hepatic hemangioma or has a history of cholestasis with prior estrogen use or during pregnancy.

12. Has a serious contraindication to pregnancy (for example, a medical condition or use of chronic medication such as isotretinoin or thalidomide).

13. History of suicidal ideation or behavior, or confirmed "yes" to any question (with exception of non-suicidal self-injurious behavior, unless deemed as an unacceptable risk by the investigator) on the C-SSRS.

14. Has a bone mineral density Z-score = -2.0 at lumbar spine, femoral neck, or total hip during the screening period.

15. Has a history of or currently has osteoporosis, or other metabolic bone disease, collagen vascular disease, chronic kidney disease (CKD) stage 3 or greater with glomerular filtration rate (GFR) < 60 mL/min/m2 using Modification of Diet in Renal Disease (MDRD) method, hyperparathyroidism, hyperprolactinemia, known pituitary adenoma, hyperthyroidism, anorexia nervosa, abnormal bone mineral metabolism (eg, hypophosphatemia), or low traumatic (fragility) fracture.

16. Has used chronic glucocorticoids that are oral, parenteral, inhaled (prednisone equivalents of = 2.5 mg daily for = 3 months) in 12 months prior to the study.

17. Has known BRCA mutation or other mutation associated with increased risk of breast cancer.

Related Conditions & MeSH terms

• Contraception
• Endometriosis
• Leiomyoma

Intervention

Drug:
• Relugolix Combination Therapy
Participants will receive orally 1 fixed-dose combination tablet (relugolix 40 mg/E2 1 mg/NETA 0.5 mg) once daily.

Locations

Country	Name	City	State
Puerto Rico	Cidra	Cidra
Puerto Rico	San Juan	San Juan
Puerto Rico	San Juan	San Juan
Puerto Rico	San Juan	San Juan
United States	Akron	Akron	Ohio
United States	Albuquerque	Albuquerque	New Mexico
United States	Annandale	Annandale	Virginia
United States	Atlanta	Atlanta	Georgia
United States	Atlanta	Atlanta	Georgia
United States	Aurora	Aurora	Colorado
United States	Austin	Austin	Texas
United States	Aventura	Aventura	Florida
United States	Baltimore	Baltimore	Maryland
United States	Bay City	Bay City	Michigan
United States	Baytown	Baytown	Texas
United States	Beaumont	Beaumont	Texas
United States	Bellevue	Bellevue	Washington
United States	Boynton Beach	Boynton Beach	Florida
United States	Brownsburg	Brownsburg	Indiana
United States	Burbank	Burbank	California
United States	Canoga Park	Canoga Park	California
United States	Chandler	Chandler	Arizona
United States	Chattanooga	Chattanooga	Tennessee
United States	Cherry Hill	Cherry Hill	New Jersey
United States	Chicago	Chicago	Illinois
United States	Chicago	Chicago	Illinois
United States	Cincinnati	Cincinnati	Ohio
United States	College Park	College Park	Georgia
United States	Columbus	Columbus	Georgia
United States	Columbus	Columbus	Ohio
United States	Columbus	Columbus	Ohio
United States	Columbus	Columbus	Ohio
United States	Covington	Covington	Louisiana
United States	Dallas	Dallas	Texas
United States	Davie	Davie	Florida
United States	Dearborn Heights	Dearborn Heights	Michigan
United States	Decatur	Decatur	Georgia
United States	Deland	DeLand	Florida
United States	Denver	Denver	Colorado
United States	Detroit	Detroit	Michigan
United States	Durham	Durham	North Carolina
United States	Encinitas	Encinitas	California
United States	Fairfield	Fairfield	Ohio
United States	Fort Worth	Fort Worth	Texas
United States	Franklin	Franklin	Ohio
United States	Gardena	Gardena	California
United States	Greenwood Village	Greenwood Village	Colorado
United States	Hialeah	Hialeah	Florida
United States	Houston	Houston	Texas
United States	Houston	Houston	Texas
United States	Houston	Houston	Texas
United States	Idaho Falls	Idaho Falls	Idaho
United States	Jackson	Jackson	Mississippi
United States	Jacksonville	Jacksonville	Florida
United States	Kissimmee	Kissimmee	Florida
United States	Lake Worth	Lake Worth	Florida
United States	Lancaster	Lancaster	California
United States	Las Vegas	Las Vegas	Nevada
United States	Las Vegas	Las Vegas	Nevada
United States	League City	League City	Texas
United States	Long Beach	Long Beach	California
United States	Long Beach	Long Beach	California
United States	Loxahatchee	Loxahatchee Groves	Florida
United States	Margate	Margate	Florida
United States	Marrero	Marrero	Louisiana
United States	Memphis	Memphis	Tennessee
United States	Memphis	Memphis	Tennessee
United States	Meridian	Meridian	Idaho
United States	Mesa	Mesa	Arizona
United States	Metairie	Metairie	Louisiana
United States	Miami	Miami	Florida
United States	Miami	Miami	Florida
United States	Miami	Miami	Florida
United States	Miami	Miami	Florida
United States	Middleton	Middleton	Wisconsin
United States	Midland	Midland	Texas
United States	Minot	Minot	North Dakota
United States	Mishawaka	Mishawaka	Indiana
United States	Mobile	Mobile	Alabama
United States	Myrtle Beach	Myrtle Beach	South Carolina
United States	Nampa	Nampa	Idaho
United States	New Bern	New Bern	North Carolina
United States	New Brunswick	New Brunswick	New Jersey
United States	New Orleans	New Orleans	Louisiana
United States	New Port Richey	New Port Richey	Florida
United States	New York	New York	New York
United States	Norcross	Norcross	Georgia
United States	Norfolk	Norfolk	Virginia
United States	Norfolk	Norfolk	Virginia
United States	North Las Vegas	North Las Vegas	Nevada
United States	Orlando	Orlando	Florida
United States	Orlando	Orlando	Florida
United States	Palo Alto	Palo Alto	California
United States	Panama City	Panama City	Florida
United States	Pearland	Pearland	Texas
United States	Peoria	Peoria	Arizona
United States	Philadelphia	Philadelphia	Pennsylvania
United States	Philadelphia	Philadelphia	Pennsylvania
United States	Phoenix	Phoenix	Arizona
United States	Portland	Portland	Oregon
United States	Raleigh	Raleigh	North Carolina
United States	Raleigh	Raleigh	North Carolina
United States	Sacramento	Sacramento	California
United States	Saginaw	Saginaw	Michigan
United States	Saginaw	Saginaw	Michigan
United States	Saint Louis	Saint Louis	Missouri
United States	Saint Louis	Saint Louis	Missouri
United States	Salt Lake City	Salt Lake City	Utah
United States	San Antonio	San Antonio	Texas
United States	San Antonio	San Antonio	Texas
United States	San Diego	San Diego	California
United States	San Diego	San Diego	California
United States	San Fernando	San Fernando	California
United States	Sandy Springs	Sandy Springs	Georgia
United States	Sarasota	Sarasota	Florida
United States	Savannah	Savannah	Georgia
United States	Seattle	Seattle	Washington
United States	Shawnee	Shawnee Mission	Kansas
United States	Shreveport	Shreveport	Louisiana
United States	Smyrna	Smyrna	Georgia
United States	Sugar Land	Sugar Land	Texas
United States	Summerville	Summerville	South Carolina
United States	Tampa	Tampa	Florida
United States	Towson	Towson	Maryland
United States	Tucson	Tucson	Arizona
United States	Valley Village	Valley Village	California
United States	Washington	Washington	District of Columbia
United States	Washington	Washington	District of Columbia
United States	Webster	Webster	Texas
United States	West Covina	West Covina	California
United States	Wichita	Wichita	Kansas
United States	Winston-Salem	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Sumitomo Pharma Switzerland GmbH

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the At-Risk Pearl Index (PI)	The At-Risk PI is defined as the number of on treatment pregnancies per 100 women-years of treatment. The At-Risk PI will be calculated on the basis of cycles considered at-risk of pregnancy, that is, consecutive 28-day periods without use of any other contraceptive methods and with affirmed occurrence of vaginal intercourse. On-treatment pregnancies are pregnancies with an estimated conception date between the first day of study intervention intake up to and including 7 days after the last intake of study medication.	13 consecutive 28-day treatment cycles
Secondary	Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the Modified At-Risk PI	The Modified At-Risk PI is based on the number of on-treatment pregnancies occurring during cycles without any other contraceptive methods, regardless of occurrence of vaginal intercourse. On-treatment pregnancies are pregnancies with an estimated conception date between the first day of study intervention intake up to and including 7 days after the last intake of study medication.	13 consecutive 28-day treatment cycles
Secondary	Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the Gross PI	The "typical use" contraceptive efficacy will be assessed using the Gross PI, based on the number of on-treatment pregnancies occurring during all cycles regardless of the use of other contraceptive methods, confirmed vaginal intercourse, or protocol compliance. On-treatment pregnancies are pregnancies with an estimated conception date between the first day of study intervention intake up to and including 7 days after the last intake of study medication.	13 consecutive 28-day treatment cycles
Secondary	Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the Method Failure PI	The "perfect use" contraceptive efficacy will be assessed using the Method Failure PI, based on the number of on-treatment pregnancies occurring during cycles that are at risk and without major protocol deviations. On-treatment pregnancies are pregnancies with an estimated conception date between the first day of study intervention intake up to and including 7 days after the last intake of study medication.	13 consecutive 28-day treatment cycles
Secondary	Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the Cumulative 1-Year Pregnancy Rates		13 consecutive 28-day treatment cycles
Secondary	Incidence of Treatment-Emergent Adverse Events		54 Weeks
Secondary	Number of Participants Who Do Not Complete 13 Treatment Cycles		13 consecutive 28-day treatment cycles
Secondary	Percent Change in Bone Mineral Density from Baseline to 6 and 12 Months On-Treatment	The percent change in bone mineral density will be measured from baseline to 6- and 12-months on treatment at the lumbar spine (L1-L4), total hip, and femoral neck.	12 Months On-Treatment or EOT
Secondary	Percent Change in Bone Mineral Density from Baseline an 12 Months On-Treatment (or EOT) to 6 and 12 Months Post-Treatment	The percent change in bone mineral density will be measured from baseline and 12-months on-treatment (or End-of-Treatment) to 6- and 12-months post-treatment at the lumbar spine (L1-L4), total hip, and femoral neck.	12 Months Post-Treatment Follow-Up